Sugar–amino acid cyclic conjugates as novel conformationally constrained hydroxyethylamine transition-state isosteres

Hydroxyethylamine (HEA) isosteres have previously been shown to display a multitude of biomedical applications. In fact, the first protease inhibitor, saquinavir is an HEA based peptidomimetic. Herein we describe an easy-to-operate synthetic route to a series of carbohydrate-based conformationally constrained hydroxyethylamine (HEA) isosteres featuring amino acid side chains, starting from d-glucose. This class of novel sugar–amino acid-tethered conformationally restricted HEA systems may have bearing in practical application, particularly in the development of conformationally restricted protease inhibitors.